P22 THE PROGNOSTIC ROLE OF 1Q ABNORMALITIES IN NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS
Authors: I. Attucci, S. Pilerci, S. Bonifacio, L. Pengue, A. Buzzichelli, M. Messeri, AM Vannucchi, E. Antonioli
Journal: HemaSphere (2023)

Background: Additional copies of chromosome 1q (+1q) is one of the most common cytogenetic abnormalities in multiple myeloma, with a frequency in newly diagnosed patients (NDMM) around 30-50%. However, its prognostic impact is still debated, since not all studies support an adverse outcome associated with +1q. Methods: In our observational retrospective study we evaluated 157 consecutive patients with NDMM between September 1, 2017 and December 31, 2020, treated at AOU Careggi Hospital in Florence. All the cytogenetic analysis were performed by fluorescence in situ hybridization (FISH), including probes for 1q abnormalities. Results: The median age in our cohort was 65, M/F=78/79. Fifty-seven patients (36.3%) had +1q abnormalities: 42 (26.7%) had 3 copies of 1q (gain 1q) and 15 (9.5%) ≥4 copies of 1q (amp1q). Patients with +1q had more frequent a concomitant high risk cytogenetic feature (26% vs 13%, p= 0,03), in particular t(4;14). The presence of additional copies of chr 1q was associated with female sex (33.3% vs 66.7%, p= 0,005), older age (median 64 vs 69), higher tumor burden (≥ 60% of plasma cells in the bone marrow, p< 0,001) and anemia (p= 0,029). There was no statistically significant difference in ISS and R-ISS classification; instead, more patients with +1q had high and intermediate-high risk disease, according to R2-ISS stratification (p< 0,001). We evaluated PFS and OS of the entire cohort after a median follow-up of 38 months: no statistically significant difference emerged in PFS and OS, between +1q patients and those without +1q. Within the cohort, 84 patients (53.5%) were eligible for autologous stem cell transplant (ASCT) and received induction with proteasome inhibitor-based therapy (i.e., VTD and VCD). Among this group the presence of +1q was, instead, associated to a reduced PFS (median PFS 40 months vs NR; p= 0,05) and OS (median OS 60 months vs NR, p= 0,009); also confirmed in multivariate analysis (p= 0,02). Moreover, 12 patients in this group eventually did not undergo transplant, due to HSC collection failure or onset of acute comorbidities; a subgroup analysis showed a worse outcome of their PFS and OS, compared to the ones who received high dose chemotherapy and HSC rescue (p< 0,001). The other 73 (46.5%) patients were ineligible for high dose chemotherapy and received predominantly bortezomib-based (VMP or VD; 59%) or lenalidomide-based treatment (Rd, 37%). The PFS and OS analysis has not revealed a significant negative impact of +1q in this group. Even if not statistically significant, a sub stratification according to different therapies in this category showed a trend of better PFS outcome for +1q patients treated with lenalidomide. Conclusions: In our study cohort +1q was associated to unfavorable outcome in patients eligible for ASCT, with only a partial reduction of this negative impact by high-dose chemotherapy. On the contrary, in older patient +1q has not proven to be an independent marker of poor prognosis, possibly due to a less intensive treatment and concomitant comorbidities which contributes to a generally reduced PFS and OS compared to the younger population.